Clinical Trials /

Pazopanib in Molecularly Selected Patients With Advanced NSCLC

NCT02193152

Description:

The purpose of this study is to evaluate how participants with advanced non-small cell lung cancer (NSCLC) that have certain abnormalities in the pazopanib target genes respond to pazopanib treatment.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Pazopanib</span> in Molecularly Selected Patients With Advanced <span class="go-doc-concept go-doc-disease">NSCLC</span>

Title

  • Brief Title: Pazopanib in Molecularly Selected Patients With Advanced NSCLC
  • Official Title: A Pilot Study of Pazopanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT02193152

    ORG ID: 201408009

    Trial Conditions

    Carcinoma, Non-Small Cell Lung

    Non-Small Cell Lung Cancer

    Nonsmall Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Pazopanib GW786034, Votrient Treatment: Pazopanib

    Trial Purpose

    The purpose of this study is to evaluate how participants with advanced non-small cell lung
    cancer (NSCLC) that have certain abnormalities in the pazopanib target genes respond to
    pazopanib treatment.

    Detailed Description

    There has been a limited benefit from anti-angiogenesis drugs in patients with NSCLC.
    Bevacizumab provides a modest survival improvement when added to chemotherapy and VEGFR
    tyrosine kinase inhibitors have been associated with minimal efficacy as single agents and
    increased toxicity when combined with chemotherapy. We postulate that the response rates and
    survival may be improved with a better selection of patients based on abnormalities of the
    targets for the drugs. According to the preliminary data from the cancer genome atlas
    (TCGA), the targets of pazopanib are altered in 28% of patients with adenocarcinoma and 24%
    of patients with squamous cell lung cancer. Since, despite the molecular selection prior to
    treatment, only a small percentage of patients will benefit from the treatment, we plan to
    further investigate those patients with whole exome sequencing in both the pre-treatment
    samples to identify the predictors for response and at the time of progression, with
    repeated biopsy, in an attempt to identify the predictors for secondary resistance. By
    identifying more reliable predictors for response to pazopanib, our study may help to
    establish its role in the treatment of NSCLC.

    Trial Arms

    Name Type Description Interventions
    Treatment: Pazopanib Experimental Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal. One cycle of pazopanib is 28 days. Pazopanib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed diagnosis of advanced (metastatic or unresectable) non-small
    cell lung cancer (NSCLC) with abnormalities in the pazopanib target genes defined as
    VEGFR1-3, PDGFRA, PDGFRB, or TP53 with abnormalities including deletion, insertion,
    early stop codon, and/or nonsynonymous mutations with functional consequences.

    - Evaluable disease by imaging or physical exam OR measurable disease defined as at
    least one lesion that can be accurately measured in at least one dimension (longest
    diameter to be recorded) as 10 mm with CT scan, as 20 mm by chest x-ray, or 10
    mm with calipers by clinical exam.

    - Failed at least one standard chemotherapeutic treatment for NSCLC.

    - At least 18 years of age.

    - ECOG performance status 2

    - Normal bone marrow and organ function as defined below:

    - Absolute neutrophil count 1,500/mcl

    - Platelets 100,000/mcl

    - Hemoglobin 9.0 g/dL

    - PT or INR 1.2 x IULN

    - aPTT 1.2 x IULN

    - Total bilirubin 1.5 x IULN

    - AST(SGOT)/ALT(SGPT) 2.5 x IULN

    - Creatinine 1.5 mg/dL OR creatinine clearance 30 mL/min/1.73 m2 for patients
    with creatinine levels above 1.5 mg/dL

    - UPC < 1 or, if UPC 1, 24-hour urine protein < 1 g; use of urine dipstick for
    renal function assessment is not acceptable.

    Notes:Subjects may not have had a transfusion within 7 days of screening assessments.
    Concomitant elevation of bilirubin and AST/ALT above the IULN is not allowed.

    - Patients receiving anticoagulation therapy are eligible if their INR is stable and
    within the recommended range for the desired level of anticoagulation.

    - Ability to swallow and retain oral tablets.

    - Women of childbearing potential and men must agree to use adequate contraception
    (hormonal or barrier method of birth control, abstinence) prior to study entry and
    for the duration of study participation. Should a woman become pregnant or suspect
    she is pregnant while participating in this study, she must inform her treating
    physician immediately.

    - Ability to understand and willingness to sign an IRB approved written informed
    consent document.

    Exclusion Criteria:

    - Treatment with any of the following anti-cancer therapies:

    - Radiation therapy, surgery, or tumor embolization within 14 days prior to the
    first dose of pazopanib OR

    - Chemotherapy, immunotherapy, biologic therapy, investigational therapy, or
    hormonal therapy within 14 days or 5 half-lives of a drug (whichever is longer)
    prior to the first dose of pazopanib).

    - Prior treatment with any VEGFR tyrosine kinase inhibitor.

    - Administration of any non-oncologic investigational drug within 30 days or 5
    half-lives (whichever is longer) prior to the first dose of pazopanib.

    - Use of a strong CYP3A4 inhibitor less than 14 days prior to initiation of study
    treatment

    - A history of other malignancy 5 years previous with the exception of basal cell or
    squamous cell carcinoma of the skin which were treated with local resection only or
    carcinoma in situ of the cervix.

    - Symptomatic brain metastases. Patients with known brain metastases are allowed if
    they are asymptomatic.

    - A history of allergic reactions attributed to compounds of similar chemical or
    biologic composition to pazopanib or other agents used in the study.

    - Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is
    progressing in severity (except alopecia).

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, uncontrolled seizure disorder, chronic underlying liver disease unrelated
    to cancer, or psychiatric illness/social situations that would limit compliance with
    study requirements.

    - Corrected QT interval (QTc) > 480 msecs.

    - History of any one or more of the following cardiovascular conditions within the past
    6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina
    pectoris, coronary artery bypass graft surgery, symptomatic peripheral vascular
    disease, class III or IV congestive heart failure as defined by the New York Heart
    Association (see Appendix B).

    - Poorly controlled hypertension (defined as systolic blood pressure of 140 mmHg or
    diastolic blood pressure of 90 mmHg). Note: initiation or adjustment of
    antihypertensive medication(s) is permitted prior to study entry. Following
    antihypertensive medication initiation or adjustment, blood pressure must be
    reassessed three times at approximately 2-minute intervals. At least 24 hours must
    have elapsed between antihypertensive medication initiation or adjustment and blood
    pressure measurement. These three values should be averaged to obtain the mean
    diastolic and systolic blood pressures, which must be < 140/90 mmHg in order for a
    patient to be eligible for the study.

    - Clinically significant gastrointestinal abnormalities that may increase the risk for
    gastrointestinal bleeding, including (but not limited to) active peptic ulcer
    disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory
    bowel disease (e.g., ulcerative colitis, Crohn's disease) or other GI conditions with
    increased risk of perforation, history of abdominal fistula or intra-abdominal
    abscess within 28 days prior to beginning study treatment.

    - Clinically significant gastrointestinal abnormalities that may affect absorption of
    pazopanib, including (but not limited to) malabsorption syndrome or major resection
    of the stomach or small bowel.

    - History of cerebrovascular accident including transient ischemic attack, pulmonary
    embolism (including asymptomatic or previously treated PE), or untreated deep venous
    thrombosis within the past 6 months. Patients with recent DVT who have been treated
    with therapeutic anti-coagulating agents for at least 6 weeks are eligible.

    - Major surgery or trauma within 28 days prior to first dose of pazopanib and/or
    presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
    placement not considered to be major surgery).

    - Evidence of active bleeding or bleeding diathesis.

    - Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that
    increase the risk of pulmonary hemorrhage. Note: lesions infiltrating major
    pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence
    of a tumor that is touching but not infiltrating (abutting) the vessels is acceptable
    (CT with contrast is strongly recommended to evaluate such lesions). Large
    protruding endobronchial lesions in the mail or lobar bronchi are excluded; however,
    endobronchial lesions in the segmented bronchi are allowed. Lesions extensively
    infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in
    the wall of thee bronchi are allowed.

    - Recent hemoptysis ( teaspoon of red blood within 8 weeks before first dose of
    pazopanib).

    - Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test
    within 14 days of study entry.

    - Known HIV-positivity. Appropriate studies will be undertaken in patients receiving
    combination antiretroviral therapy when indicated.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Response rate

    Progression-free survival (PFS)

    Secondary Outcome Measures

    Outcomes associated with specific mutations

    Mutational predictors for extreme responders

    Mechanisms of secondary resistance.

    Trial Keywords

    Advanced Non-Small Cell Lung Cancer

    NSCLC

    Pazopanib